This invention relates to an inhaler for medicament and in particular to an inhaler for transferring to the respiratory system of a patient a metered dose of medicament contained in a pressurised dispensing canister.
In known metered dose inhalers, the aerosol stream comprising liquefied propellant and medicament from a pressurised dispensing canister is fired into a chamber towards a mouthpiece of the inhaler into an air space that allows airflow travelling in the same direction via openings to the outside air. In known devices at actuation, a user inhales through a mouthpiece of the inhaler and creates an airflow through the chamber from air inlets which are generally at a part of the inhaler located upstream from the mouthpiece. Upon actuation, the medicament is then released into this airflow at a point between the air inlets and the mouthpiece so that it is travelling in the same direction as the airflow. Typically in such devices, there is little restriction in the airflow between the air inlets and the mouthpiece. Because of this, a substantial airflow may be created by a user of the device and, because the medicament is fired into the airflow in the same direction as the airflow, the effect is that particles of medicament can be travelling at quite substantial velocities e.g. in excess of 40 m/s when they reach the mouthpiece. As inhalers of this type are normally designed to be as small as practical for the convenience of users, the distance between the point at which the medicament is fired into the airflow and the patient""s mouth is usually quite small so that there is little distance to reduce the inertia of the particles of medicament with the result that the particles may impact and deposit in the oropharynx rather than being carried with inhaled air into the lungs. This is normally quite undesirable, since the medicaments were designed for delivery to the respiratory system and may not have an appropriate effect when deposited in the oropharynx and allowed to enter the digestive tract.
In an effort to overcome this problem, devices have been produced in which the medicament is fired into a holding volume, commonly called a Spacer, which allows the velocity of the medicament to be reduced and also allows some propellant evaporation to occur. Spacers can improve the performance of a metered dose inhaler by reducing oropharyngeal deposition, see S. P. Newman and S. W. Clarke, Chest, vol 103 (5) pp. 1442-1446 (1993) Bronchodilator Delivery From Gentlehaler, A New Low-Velocity Pressurized Aerosol Inhaler and S. P. Newman, A. R. Clark, N. Talee and S. W. Clarke, Thorax, vol 44 pp.706-710 (1989), Pressurised aerosol deposition in the human lung with and without an xe2x80x9copenxe2x80x9d spacer device.
However, these devices with a holding volume and other spacer devices tend to be of significantly larger size than the conventional metered dose inhalers and therefore less convenient and attractive to users.
Various attempts have been made to modify the spray characteristics of inhalers.
GB-A-2279879 discloses an inhaler in which the air inlets are arranged such that during inhalation an airflow is created which has a component directed away from the mouthpiece towards the aerosol spray. The reverse airflow component is intended to create turbulence and slow the velocity of the medicament particles.
WO93/05837 and U.S. Pat. No. 4,972,830 disclose inhalers in which the passage which directs the pressurised medicament from the canister to the chamber has particular configurations to reduce the velocity of the spray and enhance dispersion of the medicament in the airflow.
EP-A-0412648 discloses an inhaler in which a frusto-conical diverter with a small orifice is positioned in the path of the spray before the mouthpiece. Aerosol droplets are said to predominantly pass through the small orifice, decelerate and be inhaled while the propellant gas is predominantly diverted away from the mouthpiece out of the inhaler.
It is known to modify the airflow through an inhaler to achieve particular effects. WO93/09830 discloses an inhaler which is constructed and arranged to prevent inhalation through the device prior to the dose being fired. The object of the arrangement is to synchronise inhalation and firing the dose to ensure the dose is dispensed during inhalation. U.S. Pat. No. 5,758,638 discloses an inhaler which includes an air port so that during inhalation flow of air through the port activates an audio or visual signal generates, such as a whistle or flag, that signals to the user that the user is inhaling and that the conditions are appropriate for the administration of the medicament.
Similarly for intranasal inhalers it is desirable to reduce the velocity of the spray in the interests of patient comfort and efficacity.
The present invention provides alternative constructions of an inhaler which reduce the velocity of the spray exiting the mouthpiece or nasal adapter.
According to the present invention there is provided an inhaler for medicament comprising an aerosol canister containing a pressurised medicament formulation equipped with a metered dose dispensing valve having a valve stem movable between non-dispensing and dispensing positions, and an actuator comprising a housing adapted to receive the aerosol container and defining a chamber having one or more air inlets and a patient port in the form of a mouthpiece or nasal adapter, and a nozzle block adapted to receive the valve stem of the dispensing valve, the nozzle block comprising a passage in communication with the valve stem and terminating in an orifice for directing medicament from the valve stem into the chamber, in which the actuator is constructed and arranged to inhibit patient-induced airflow in the vicinity of the orifice of the nozzle block when the valve stem is in its dispensing position.
The inhaler of the invention may be constructed such that airflow due to patient inhalation is prevented or reduced in the vicinity of the orifice at all times or only during dispensing of the medicament from the valve. Either arrangement has the effect of substantially reducing the velocity of the emitted spray compared to an inhaler which allows free flow of air in the vicinity of the nozzle block during dispensing of the medicament. It is possible to modify existing press and breathe inhalers to prevent such airflow by the provision of a suitable gasket.
It has been discovered that the velocity of an aerosol spray from a metered dose inhaler is significantly influenced by the presence of an open conduit in the vicinity of the nozzle through which the spray emerges. The spray exits the nozzle as a high velocity stream which creates low pressure regions. The ability of the free-flowing air entering through air vents to fill the low pressure regions influences the velocity of the emitted spray. If a free flow of air is allowed in the vicinity of the nozzle, as in a standard press-and-breathe inhaler where the patient breathes through the mouthpiece and an airflow is established around the canister and nozzle to the mouthpiece, the emitted spray maintains a high velocity. If the actuator is sealed to outside airflow in the vicinity of the nozzle, the low pressure regions cannot immediately be occupied by the surrounding air and the low pressure regions exert a retarding influence on the stream emanating from the nozzle, thereby causing the stream to lose velocity.
It has been found that inhibiting make-up, or free-flowing air in the vicinity of the nozzle when the spray is generated significantly reduces the velocity of the emitted spray and spray force from the mouthpiece, resulting in an extremely soft, low velocity spray plume.
The vicinity of the orifice includes on all sides upstream to the temporary or permanent closure behind the nozzle block, and downstream to the first communication with the outside atmosphere. That is, during dispensing there is no communication to the outside atmosphere for the region surrounding the orifice of the nozzle block. There is no communication with the outside atmosphere via the air inlets upstream to the orifice of the nozzle block and no communication with the outside atmosphere downstream of the orifice of the nozzle block for a distance sufficient to allow the aerosol stream to develop sufficient turbulence to stop its downstream momentum. For example, the stream exiting 0.30 mm to 0.50 mm orifice would not be in communication with the outside atmosphere via the upstream air inlets and the stream would be in communication with outside air being drawn into the device at a downstream distance relative to the orifice of 4 to 6 cm. The location downstream of the orifice at which the outside air is drawn into the device may vary from 0 to 15 cm depending on the orifice diameter and mouthpiece diameter.
Radioscintigraph tests have revealed that when airflow is prevented or restricted in the vicinity of the nozzle the flow of the spray becomes turbulent within the chamber. The turbulent zone is generally formed between about 3 to 5 cm from the nozzle for a nozzle orifice of approximately 0.30 mm. The high degree of turbulence causes a large reduction in the linear velocity of the spray as well as an increase in the deposition of drug particles on the wall of the chamber. If the chamber and mouthpiece are of sufficient length to encompass this turbulent zone the result is a significant reduction in the kinetic energy of the stream delivered to the patient. Preferably, the actuator is constructed such that the distance from the nozzle to the mouthpiece is from approximately 1 to 15 cm, preferably 4 to 6 cm, with a chamber/mouthpiece diameter from 1 to 4 cm, 0.5 to 1 cm in the case of a nasal adapter.
The actuator must possess air inlets which enable the patient to inhale though the patient port without encountering significant resistance since the patient may have breathing difficulties when taking the medication e.g. during an asthma attack. However, the air inlets, for example in the mouthpiece, must not concentrate the airflow into too narrow an area, as this will give a high velocity of incoming air which will deflect the spray onto the wall of the mouthpiece opposite the air inlets.
In one embodiment of the invention the air inlets are positioned downstream of the nozzle, in the region of the turbulent zone and/or downstream of the turbulent zone. The positioning and direction of the air inlets may also affect the deposition of medicament within the chamber and mouthpiece. In one arrangement air inlets comprise a series of holes, within or downstream of the turbulent zone adjacent the mouthpiece directing air perpendicular to the aerosol stream. In a second arrangement the air inlets are directed towards the outlet of the mouthpiece to introduce a sheath of air around the aerosol stream, parallel to the aerosol stream. In a third arrangement the air inlets are arranged, optionally interdispersed with baffles on the wall of the chamber, to direct air into the turbulent zone to mix air with the aerosol stream. In a fourth arrangement the air inlets are positioned at the downstream end or downstream of the turbulent zone and direct air back towards the turbulent zone. In a further arrangement a mouthpiece is constructed of porous material to allow a multiplicity of finely divided air vents to provide air flow over a larger surface area. The diffuse airflow through the mouthpiece also tends to keep the formulation stream away from the mouthpiece wall, thereby reducing drug deposition on the walls.
In a second embodiment of the invention the actuator may possess air inlets upstream of or in the vicinity of the nozzle but the air inlets are blocked when the valve is fired to release the aerosol spray. The air inlets are opened after the spray has been released by which time the velocity of the stream will have been reduced and the turbulent zone formed. Upon inhalation an airflow will be established from the air inlets to the mouthpiece which entrains the residual aerosol spray. The actuator may include additional air inlets downstream of the nozzle, as described above with respect to the first embodiment. These downstream air inlets do not need to close during release of the aerosol spray.
A third embodiment uses a porous membrane to introduce air into or downstream of the turbulent zone. The advantage of the membrane is that the air is introduced more uniformly and diffusely around the circumference of the spray, thereby acting as a buffer between the turbulent flow and the wall. The effect is to reduce drug deposition in the device. The membrane may optionally be protected from dirt or contact by the users lips by an additional part of the mouthpiece. This embodiment may be used in combination with embodiment 1 or 2. Additionally, this embodiment may be incorporated without the restricting or preventing of airflow in the vicinity of the nozzle.
For certain medicaments it is particularly desirable to reduce contact between the medicament and parts of the body it is not intended for. For example, residues of the medicament deposited on internal surfaces of actuators may be fingered and transferred to other body parts. A fourth embodiment of the invention incorporates a baffle to allow the spray to pass through, whilst limiting access by the patient to internal surfaces of the actuator.
A fifth embodiment of the invention is configured for intranasal delivery.
It is known that the size of the orifice in the nozzle may affect the spray characteristics. Smaller orifices tend to produce aerosols of small droplet size which lead to improved respirable fraction. However, smaller orifices are more difficult to manufacture. The actuator of the invention significantly reduces the spray velocity regardless of the orifice size. It has been shown to reduce oropharyngeal deposition with orifices in the size range 0.010 to 0.025 inch and the deposition for these two sizes was found not to differ significantly.